A phase I multicentric trial of combined chemotherapy with gemcitabine plus S-1 in patients with advanced pancreatic cancer

14047 Background: While gemcitabine (GEM) is the standard drug for chemotherapy against advanced pancreatic cancer, the development of multidrug therapies for improved outcome is important. We conducted multicentric combined chemotherapy with GEM and S-1 and report the results of the phase I trial. Methods: The subjects had unresectable pancreatic ductal cancer. The method of administration was single administration of GEM on the first day of the week from Level 1 to Level 4 at 400 to 1000 mg/m2, with concurrent administration of S-1 at 40 to 100 mg/day × 7 days, repeated every other week as a collaborative trial conducted at 3 facilities. The purpose was to determine the optimal dose with adverse events as an indicator. Results: Eighteen patients were enrolled (3 each at Levels 1, 2, 3 and 4’, 6 at Level 4). Average age was 60.9 years (38 - 71 years). There was no dose limiting toxicity (DLT) up to Level 3. Level 4 was the maximum tolerated dose since DLT was observed in 4/6 patients (mucositis 2, rash 1, anorexia 1), and no DLT was observed in 3 additional patients at Level 4’. The resulting recommended dose was Level 4 (GEM 1000 mg/m2, S-1 100 mg/day). For reference, partial response was observed in 5 patients, and median survival time at this stage is 336±39 days. Conclusions: The recommended dosage of GEM + S-1 combined chemotherapy for unresectable advanced pancreatic cancer was determined in a phase I trial. We intend to proceed to a phase II trial. No significant financial relationships to disclose.

Download Full-text

A phase II multicentric trial of combined chemotherapy with gemcitabine plus S-1 in patients with advanced pancreatic cancer

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.15129 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 15129-15129

Author(s):

S. Ohkawa ◽

A. Amano ◽

M. Ueno ◽

K. Miyakawa ◽

K. Sugimori ◽

...

Keyword(s):

Pancreatic Cancer ◽

Phase I ◽

Survival Time ◽

Median Survival ◽

Phase Ii ◽

Median Survival Time ◽

Progressive Disease ◽

Advanced Pancreatic Cancer ◽

Combined Chemotherapy ◽

Standard Drug

15129 Background: While gemcitabine (GEM) is the standard drug for chemotherapy against advanced pancreatic cancer, the development of multidrug therapies for improved outcome is important. We conducted multicentric combined chemotherapy with GEM and S-1 trial and reported the results of the phase I trial last year. And this phase II study evaluated the efficacy and feasibility. Methods: The subjects had unresectable pancreatic ductal cancer. Eligibility criteria were pathologically-proven, Karnofsky performance status 80 to 100%, age 20 to 74 years, adequate hematological, renal, and liver functions and written informed consent. The method of administration was single administration of GEM on the first day of the week 1000 mg/m2, with concurrent administration of S-1 at 80 (<1.5 m2) to 100 (=1.5 m2) mg/day × 7 days, repeated every other week until the progressive disease or life threatening adverse events. This administration dose was determined from the result of the phase I study. The primary endpoint was median survival time. And the secondary endpoints were the overall response rate and the toxicities. Results: 40 patients(pts) were enrolled. Average age was 62.9±8.3 years (34–73 years). Thirty nine pts were conducted this therapy except one who refused this study before the start of administration. Thirty eight pts were evaluable for response, partial response, stable disease, progressive disease were observed in 7 (17.5%), 21 (52.5%) and 10 pts (25.0%), respectively. The median survival time at this stage is 276±51 days in this ongoing study. Grade 3 and 4 toxicities were mainly leucocytes(10 pts), neutrophils(8 pts) and anorexia(6 pts). Conclusions: The GEM plus S-1 combined chemotherapy is effective and feasible in patients with advanced pancreatic cancer. No significant financial relationships to disclose.

Download Full-text

FOLFOX and nab-paclitaxel (nab-P) for advanced pancreatic cancer: A phase I study.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.3_suppl.258 ◽

2014 ◽

Vol 32 (3_suppl) ◽

pp. 258-258

Author(s):

Howard Safran ◽

Kevin Charpentier ◽

Kimberly Perez ◽

Kalyan Mantripragada ◽

Trevor Clark Austin ◽

...

Keyword(s):

Pancreatic Cancer ◽

Phase I ◽

Dose Level ◽

Phase I Study ◽

Locally Advanced ◽

Advanced Pancreatic Cancer ◽

Maximum Tolerated Dose ◽

Level 3 ◽

Grade 3 ◽

Level 2

258 Background: FOLFIRINOX improves survival in advanced pancreatic cancer, however the contribution of irinotecan is uncertain. The addition of irinotecan to gemcitabine was not superior to gemcitabine alone in pancreatic cancer, however nab-P demonstrates a survival benefit. This phase I study was designed to evaluate the maximum tolerated dose (MTD) of the addition of nab-P to fluorouracil, leucovorin, oxaliplatin (FOLFOX-A). Methods: Patients with metastatic or locally advanced pancreatic adenocarcinoma without prior treatment received oxaliplatin, 85 mg/m2, leucovorin 400 mg/m2 and 5-FU 2400 mg/m2 with 3 dose levels of nab-P (125, 150 and 175 mg/m2) every 2 weeks. Pegfilgrastim was required during the first 2 cycles. Dose limiting toxicities (DLTs) were defined in the first 2 cycles of treatment. Results: Fifteen patients were entered: Dose level 1 (n=6), dose level 2 (N=6), dose level 3 (N=3). The median age was 64 (35-81). Ten patients had metastatic and 5 had locally advanced disease. DLTs of nausea and fatigue occurred in 2 of 3 patients at dose level 3. Two patients developed grade 3 neuropathy after >= 10 cycles of treatment. One patient had grade 3/4 neutropenia. Eight of fifteen patients (53%) had a partial response. Conclusions: The MTD of nab-P is 150mg/m2 every 2 weeks with FOLFOX. Cumulative peripheral neuropathy, similar to other FOLFOX regimens, is the most significant toxicity generally occurring after >= 10 cycles of treatment. FOLFOX-A has substantial activity and may represent a promising regimen in pancreatic cancer. Patients are currently being accrued to an expansion phase utilizing dose level 2. Supported by the Davis and Browning families and LIFEcycle. Clinical trial information: NCT01744353.

Download Full-text